1. Field of the Invention
The present invention is related to the identification and characterization of a hitherto unidentified human gene, hGC-1. The invention relates generally to the gene (hGC-1), nucleotide sequences, vectors, polypeptides, antibodies, and other compositions related to hGC-1. Additionally, primers are provided for identifying hGC-1. The invention further relates to methods of using these compositions, such as diagnosis and treatment of various cancers, and kits comprising these compositions.
2. Background
During the process of hematopoiesis, pluripotent hematopoietic stem cells become committed to one lineage and eventually differentiate into functional, morphologically distinct end-stage cells (Akashi, K., Traver, D., Miyamoto, T. & Weissman, I. L. (2000) Nature 404, 193-7). In the bone marrow, pluripotent stem cells differentiate into either the lymphoid stem cell line, where they are further induced to differentiate into B- or T-derived lymphocytes, or the myeloid stem cell (CFU-GEMM) line, where they are further induced to become erythrocytes, granulocytes (neutrophils, eosinophils, or basophils), macrophages, or megakaryocytes (platelets).
Proliferation and differentiation of blood cells in the bone marrow are regulated by hematopoietic factors. Hematopoietic factors that are continuously produced include erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO). EPO, G-CSF and TPO bind to their corresponding receptors, thereby inducing tyrosine phosphorylation of a number of cellular proteins and activating specific intracellular signaling cascades, including the signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) pathways (Tidow, N. & Welte, K. (1997) Curr Opin Hematol 4, 171-5; Wojchowski, D. M., Gregory, R. C., Miller, C. P., Pandit, A. K. & Pircher, T. J. (1999) Exp Cell Res 253, 143-56; Alexander, W. S. (1999) Growth Factors 17, 13-24). Differentiation in response to hematopoietic factor signaling is accompanied by coordinate expression of specific genes. However, knowledge about the differences in the signal transduction pathways and gene expression profiles stimulated by these three hematopoietic factors remains limited.
Identification of elements that regulate hematopoietic differentiation and of the genes expressed in response to such regulators is an active area of research. For example, genetic studies in mice have revealed critical lineage-specific roles for transcriptional regulators such as C/EBP (Zhang, D. E., Zhang, P., Wang, N. D., Hetherington, C. J., Darlington, G. J. & Tenen, D. G. (1997) Proc Natl Acad Sci USA 94, 569-74), GATA-1 (Pevny, L., Lin, C. S., D'Agati, V., Simon, M. C., Orkin, S. H. & Costantini, F. (1995) Development 121, 163-72), PU.1 (Scott, E. W., Simon, M. C., Anastasi, J. & Singh, H. (1994) Science 265, 1573-7), and many others (Ness, S. A. & Engel, J. D. (1994) Curr Opin Genet Dev 4, 718-24). Elucidation of the genetic alterations underlying certain leukemias, including chromosomal translocations and more subtle mutations, has revealed the hematopoietic functions of proteins such as PLZF and AML-1 (Shivdasani, R. A. & Orkin, S. H. (1996) Blood 87, 4025-39).
A mRNA differential display approach was used to examine potentially novel genes associated with hematopoietic lineage commitment and to explore new lineage-specific markers for monitoring lineage differentiation. One of these cDNA fragments derived from differentiation pathways of various lineages was cloned and sequenced. hGC-1 (human G-CSF-stimulated clone-1), is selectively expressed in normal human myeloid lineage cells and is a marker for various cancers.
The following describes the identification and characterization of the hGC-1 gene, its induction properties in hematopoietic cells, and potentially important aspects of its corresponding extracellular protein/glycoprotein structure. Additionally, related compositions and methods for using those compositions are described.